T cells are our first line of defense against cancer, but the battle tends to exhaust them. Now, scientists have found a way to give them extra “batteries” to keep them fighting longer, with promising early results in mice.
In a fair fight, the immune system would wipe out cancer every time – but this crafty disease doesn’t play fair. Along with its many tricks to avoid detection, tumors build microenvironments around themselves that are toxic to immune cells, draining them of energy. Sustained immune responses against a pathogen like cancer can lead to T cell exhaustion.
Finding ways to supercharge the immune system to continue the fight is the main goal of immunotherapy. Now, a team from Brigham and Women’s Hospital has demonstrated a new way to refresh T cells, by essentially replacing their batteries.
Mitochondria are organelles that produce chemical energy for cells, but during T cell exhaustion these little batteries can be lost or damaged. Previous studies have shown that cancer cells can use nanotubes like “tiny tentacles” to slurp up mitochondria from immune cells. For the new study, the researchers found that they could use the same mechanism to do the opposite – donate new mitochondria to T cells, from bone marrow stromal cells (BMSCs).
The team cultured BMSCs and T cells together, and after 48 hours found that up to a quarter of the T cells had gained extra mitochondria. The researchers dubbed these juiced up immune cells Mito+.
In tests in mice, Mito+ cells were found to more easily penetrate tumors and launch a more robust attack on them. Tumors shrank drastically, and 75% of treated mice survived the full 60-day study period. In contrast, control mice saw their tumors continue to grow, and all had died by the 20-day mark.
Intriguingly, Mito+ cells could multiply quickly and pass their extra mitochondria to the new cells. Other immune cells, such as lymphocytes and CAR-Ts, also showed improved cancer-killing abilities after receiving extra mitochondria.
“These supercharged T cells overcome one of the fundamental barriers of immunotherapy by penetrating the tumor and overcoming immune barren state in the tumor,” said Shiladitya Sengupta, corresponding author of the study. “Mitochondria provide the fuel. It’s like we’re taking T cells to the fuel station and gassing them up. This transplanting of mitochondria is the dawn of organellar therapy – where an organelle is delivered to a cell to make it more effective.”
The team says that in future, BMSCs could be taken from patients and used to supercharge their own immune cells, which are then returned to the body to fight their cancer more effectively.
The research was published in the journal Cell.
Source: Brigham and Women’s Hospital